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Identification in traditional herbal medications and confirmation by synthesis of factors that inhibit cholera toxin-induced fluid accumulation.

Abstract
Kampo formulations are traditional herbal medications used in China and Japan for many centuries to treat diarrheal diseases such as cholera. Our studies were undertaken to identify and verify by chemical synthesis the active components that inhibited cholera toxin (CT), the virulence factor secreted by Vibrio cholerae, the causative agent of cholera. The Kampo formulation, Daio-kanzo-to, inhibited CT activities (i.e., ADP-ribosylation, Chinese hamster ovary cell elongation); in Daio-kanzo-to, Daio (Rhei rhizoma) was responsible for this effect. Among several components purified from Daio extract, rhubarb galloyl-tannin, a compound characterized by a polygallate structure, was the most effective. To define the active component, gallate analogues similar to rhubarb galloyl-tannin were synthesized. These gallate compounds inhibited all CT activities including ADP-ribosylation, elongation of Chinese hamster ovary cells, and importantly, fluid accumulation in ileal loops. Thus, Kampo formulations or their gallate components might be effective adjunctive therapy with oral rehydration solution for the severe diarrhea of cholera.
AuthorsHiroshi Oi, Daisuke Matsuura, Masami Miyake, Masamiti Ueno, Izumi Takai, Takeshi Yamamoto, Masayoshi Kubo, Joel Moss, Masatoshi Noda
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 99 Issue 5 Pg. 3042-6 (Mar 05 2002) ISSN: 0027-8424 [Print] United States
PMID11854470 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drugs, Chinese Herbal
  • Plant Extracts
  • Tannins
  • Adenosine Diphosphate Ribose
  • Gallic Acid
  • Cholera Toxin
Topics
  • Adenosine Diphosphate Ribose
  • Animals
  • CHO Cells
  • Carbohydrate Sequence
  • Cholera Toxin (metabolism)
  • Cricetinae
  • Drugs, Chinese Herbal (pharmacology)
  • Gallic Acid (chemical synthesis, pharmacology)
  • Herbal Medicine
  • Ileum
  • Medicine, Kampo
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Molecular Structure
  • Plant Extracts (pharmacology)
  • Rabbits
  • Tannins (chemical synthesis, pharmacology)
  • Vibrio cholerae

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